This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Gap junctions play important roles in cerebellar neurodegeneration. Protein kinase C gamma (PKCgamma) is a neuronal specific PKC. Activated PKCgamma phosphorylates and inhibits gap junctions, a process which is controlled by a cell oxidative state. Mutations in PKCgamma cause spinocerebellar ataxia type 14 (SCA-14), an autosomal, dominant neurodegenerative disorder in humans with onset ages of three to thirty years. In this proposal we will determine how gap junctions are controlled by PKCgamma activation and what the effect of inhibition of gap junctions on neural apoptosis. We will also characterize the defects in cerebellar response to oxidative stress in the PKCgamma H101Y SCA14 transgenic mouse models. Overexpression of the PKCgamma H101Y SCA14 mutation leads to significant loss of Purkinje cells in transgenic mice due to improper control of gap junctions by PKCgamma mutants.